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Updated: Aug 10, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Resistance to anti-VEGF agents
1Department of Medical Oncology, Cancer Research UK, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. Nton@picr.man.ac.uk
Abstract:
The number of anti-angiogenic agents developed for clinical use has risen greatly over the past decade. Currently, more than 80 are in trials ranging from phase I through to phase III studies and many more are in preclinical evaluation. Much hope was envisaged for these new agents to become the panacea of anti-tumoural treatment. Unfortunately the single agent activity to date has proven to be disappointing although one trial has recently reported a survival advantage when chemotherapy was administered with anti-VEGF antibodies in the setting of advanced colorectal cancer. To an extent, this may be due to great expectations of cytostatic compounds, but recently many factors have been examined to explain the differences between clinical and experimental findings. In this review, some of the factors responsible for the discrepancy are examined, with a specific focus on inhibitors of VEGF. The key factors responsible for the lack of activity are tumour heterogeneity and redundancy in the VEGF signalling system. An increased understanding of these factors is critical to the development of effective anti-angiogenic agents and need to be taken into account as new generations of drugs emerge.
Insights
Anti-angiogenic agents show disappointing single-agent activity due to tumor heterogeneity and VEGF signaling redundancy. Understanding these factors is crucial for developing effective anti-cancer therapies.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- The development of anti-angiogenic agents for cancer treatment has surged, with over 80 agents in clinical trials.
- Significant expectations were placed on these agents as a potential panacea for anti-tumoural treatment.
Purpose of the Study:
- To review factors contributing to the discrepancy between experimental and clinical findings for anti-angiogenic agents.
- To specifically examine inhibitors of Vascular Endothelial Growth Factor (VEGF) and their efficacy.
Main Methods:
- Review of current literature on anti-angiogenic agents in clinical and preclinical development.
- Analysis of factors influencing the activity of VEGF inhibitors in cancer therapy.
Main Results:
- Single-agent activity of anti-angiogenic therapies has been largely disappointing to date.
- A recent trial showed a survival advantage when chemotherapy was combined with anti-VEGF antibodies in advanced colorectal cancer.
- Tumor heterogeneity and redundancy in the VEGF signaling system are identified as key factors limiting efficacy.
Conclusions:
- Understanding tumor heterogeneity and VEGF pathway redundancy is critical for advancing anti-angiogenic drug development.
- Future generations of anti-angiogenic drugs must account for these biological complexities to improve patient outcomes.
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